The present invention relates to benzoic acid derivatives useful as intermediates for the preparation of drugs and agricultural chemicals, particularly compounds having herbicidal activity, and to processes for the preparation thereof.
A method (A) of obtaining benzoic acid derivatives by reactions represented by the following reaction scheme, 
between bicycloheptenone derivatives substituted with carboxylates and alcolates or the like is described in Tetrahedron, 42, 1741 (1986) and J. Org. Chem., 26, 2066 (1961).
However, there are no reports on reactions of bicycloheptenone derivatives substituted with hetero rings.
Known methods of dehalogenation of aromatic halogenated compounds include, for example, catalytic hydrogenolysis using palladium-carbon or Raney nickel as a catalyst, a method of using metal and metal salts such as lithium or sodium, hydrogenolytic reduction with tin hydride, reduction with metal-hydrogen complex compounds such as lithium aluminum hydride, and electrolytic reduction, which are described in Shin Jikkenkagakukouza, Vol. 14, Syntheses and Reactions of Organic Compounds [I] pages 22-30 (edited by the Chemical Society of Japan, published by Maruzen Co., Ltd.).
Substituted benzoic acid compounds, such as 4-alkylthiobenzoic acid derivatives, are important as intermediates for the preparation of agricultural chemicals and drugs. It has been desired to develop easy and industrially advantageous processes for the preparation of the said benzoic acid derivatives.
The present invention is directed to
(a) a benzoic acid derivative represented by Formula (1) 
xe2x80x83(wherein R1 is hydrogen or C1-4 alkyl,
R2 is hydrogen or C1-6 alkyl, and
Q is an optionally substituted, saturated or unsaturated, 5- or 6-membered heterocyclic group containing 1 to 4 N, O or S atoms and combining with the benzene ring via a carbon atom);
(b) a process for the preparation of a benzoic acid derivative of the said Formula (1), characterized by acting a base on a bicycloheptenone derivative of Formula (2) 
xe2x80x83(wherein R1 and Q are as defined above), in an appropriate solvent;
(c) a process for the preparation of a benzoic acid derivative of the said Formula (1), characterized by consisting of a stage of preparing a bicycloheptenone derivative of the said Formula (2) by hydrolysis of a bicycloheptene derivative of Formula (3) 
xe2x80x83(wherein R1 are as defined above, and X is chlorine or C1-4 alkoxy and two X""s may join to form a C2-3 alkylenedioxy group optionally substituted with C1-4 alkyl), and of acting a base and water or alcohol on a bicycloheptenone derivative of the said Formula (2) in an appropriate solvent;
(d) a process for the preparation of a bicycloheptene derivative of the said Formula (3), characterized by reacting a cyclopentadiene derivative of Formula (4) 
xe2x80x83(wherein X is as defined above) with an ethylene derivative substituted with a hetero ring, of Formula (5) 
xe2x80x83(wherein R1 and Q are defined above);
(e) a bicycloheptenone derivative of the said formula (2); and
(f) a process for the preparation of a benzoic acid derivative of Formula (6) 
xe2x80x83(wherein R1, R2 and Q are as defined above and R4 is C1-6 alkyl), characterized by reacting a 4,5-dichlorobenzoic acid derivative of the said Formula (1), with a mercaptan of Formula R4SH (wherein R4 is as defined above) and a base or with a salt of mercaptan of Formula R4SH (wherein R4 is as defined above)
In the definitions of the compounds of the said Formulae (1) and (2), which are the compounds of the present invention, the compounds of Formula (3) of their precursors and the compounds of Formula (6),
R1 is hydrogen, or C1-4 alkyl such as methyl, ethyl, propyl, isopropyl n-butyl isobutyl s-butyl or t-butyl;
a R2 is hydrogen, or C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl or isohexyl;
X is halogen such as chlorine, or C1-4 alkoxy such as methoxy, ethoxy, propoxy, isopropoxy or butoxy;
Two X""s may join to form a C2-3 alkylenedioxy group, such as ethylenedioxy or trimethylenedioxy;
Further, the said C2-3 alkylenedioxy group may be substituted with C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl and t-butyl; and
Q is an optionally substituted, saturated or unsaturate 5- or 6-membered heterocyclic group containing 1 to 4 N, O or S atoms and combining with the benzene or bicycloheptane ring via a carbon atom.
Such hetero rings include, for example, 5-membered heterocyclic groups containing 1 to 4 N, O or S atoms, such as
2-furyl, 3-furyl,
2-thienyl, 3-thienyl,
2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,3-dihydrofuran4-yl,2,3-dihydrofuran-5-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl,
2,3-dihydrothiophen-2-yl, 2,3-dihydrothiophen-3-yl, 2,3-dihydrothiophen-4-yl, 2,3-dihydrothiophen-5-yl, 2,5-dihydrothiophen-2-yl, 2,5-dihydrothiophen-3-yl,
pyrrol-2-yl, pyrrol-3-yl,
imidazol-2-yl, imidazol-4-yl, imidazol-5-yl,
2-imidazolin-2-yl, 2-imidazolin-4-yl, 2-imidazolin-5-yl,
pyrazol-3-yl, pyrozol-4-yl, pyrazol-5-yl,
oxazol-2-yl, oxazol-4-yl, oxazol-5-yl,
isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl.
1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,5-oxadiazol-3-yl,
4-thiazolyl, 4-thiazolyl, 5-thiazolyl,
isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl,
1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,5-thiadiazol-3-yl,
1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,3,4-triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, tetrazol-5-yl,
2-pyrrolin-1-yl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 2-pyrrolin4-yl, 2-pyrrolin-5-yl,
2-oxazolin-2-yl, 2-oxazolin-4-yl, 2-oxazolin-5-yl, 3-oxazolin-2-yl, 3-oxazolin-4-yl, 3-oxazolin-5-yl, 4-oxazolin-2-yl, 4-oxazolin-4-yl, 4oxazolin-5-yl,
2-isoxazolin-3-yl, 2-isoxazolin-4-yl, 2-isoxazolin-5-yl,
3-isoxazolin-3-yl, 3-isoxazolin-4-yl, 3-isoxazolin-5-yl,
4-isoxazolin-3-yl, 4-isoxazolin-4-yl, 4-isoxazolin-5-yl,
2-thiazolin-2-yl, 4-thiazolin-4-yl, 4-thiazolin-5-yl,
2-isothiazolin-3-yl, 2-isothiazolin-4-yl, 2-isothiazolin-5-yl,
3-isothiazolin-3-yl, 3-isothiazolin-4-yl, 3-isothiazolin-5-yl,
4-isothiazolin-3-yl, 4-isothiazolin-4-yl, 4-isothiazolin-5-yl,
1-pyrazolin-3-yl, 1-pyrazolin-4-yl, 1-pyrazolin-5-yl,
2-pyrazolin-3-yl, 2-pyrazolin-4-yl, 2-pyrazolin-5-yl,
3-pyrazolin-3-yl, 3-pyrazolin-4-yl and 3-pyrazolin-5-yl; saturated 5-membered heterocyclic groups containing 1 to 4 N, O or S atoms, such as
2-pyrrolidinyl, 3-pyrrolidinyl,
2-tetrahydrofuranyl, 3-tetrahydrofuranyl,
2-tetrahydrothienyl, 3-tetrahydrothienyl,
2-oxazolidinyl, 4-oxazolidinyl, 5-oxazolidinyl,
3-isoxazolidinyl, 4-isoxazolidinyl, 5-isoxazolidinyl,
2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl,
3-isothiazolidinyl, 4-isothiazolidinyl, 5-isothiazolidinyl,
2-imidazolidinyl, 4-imidazolidinyl,
1,2,4-oxadiazolidin-3-yl, 1,2,4-oxadiazolidin-5-yl, 1,3,4-oxadiazolidin-2-yl,
1,2,4-thiadiazolidin-3-yl, 1,2,4-thiadiazolidin-5-yl, 1,3,4-thiadiazolidin-2-yl,
1,3,4-triazolidin-2-yl,
1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl,
1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, and
1,3-oxathiolan-2-yl; and
6-membered heterocyclic groups containing 1 to 4 N, O or S atoms, such as
2-pyridyl, 3-pyridyl, 4-pyridyl,
3-pyridazinyl, 4-pyridazinyl,
2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
pyrazin-2-yl,
2H-pyran-3-yl, 2H-thiopyran-3-yl,
2-piperidinyl, 3-piperidinyl, 4-piperidinyl
2-piperadinyl,
2-morpholinyl, 3-morpholinyl,
5,6-dihydro-4H-1,3-thiazin-2-yl,
2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,
2-tetrahydrothiopyranyl, 3-tetrahydrothiopyranyl and 4-tetrahydrothiopyranyl.
These groups may have one or more, same or different, substituents at arbitrary positions of the hetero rings. Such substituents include, for example, C1-4 alkyl such as methyl, ethyl, propyl isopropyl, n-butyl, isobutyl, s-butyl and t-butyl, and C1-4 haloalkyl such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl and pentafluoroethyl.
Q is more preferably one of the following groups represented by Q-1 to Q-9. 
In the above formulae, R3 is, for example, C1-4 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, s-butyl or t-butyl, or C1-4 haloalkyl such as chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl or pentafluoroethyl, and n is 0 or an integer of 1 or 2.
Further, in the said Formula (6), R4 is C1-6 alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl s-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl or isohexyl.
The compounds of the present invention, represented by the said Formulae (2) and (3), may have stereoisomers, depending on substituents at positions 5 and 6. They are all covered by the present invention.
The compounds of the present invention may be produced by the following processes:
(Process 1) Process for the Preparation of a 4,5-dichlorobenzoic Acid Derivative from a Bicycloheptenone Derivative 
(wherein R1, R2 and Q are as defined above).
A bicycloheptenone derivative (2) of Formula (2) is reacted with a base and water or alcohol in an appropriate solvent to give a compound of Formula (1).
Bases used for this reaction include, for example, alkali metal alcolates such as sodium methylate, sodium ethylate and potassium t-butoxide; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as calcium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate and sodium hydrogen carbonate; and alkaline earth metal carbonates.
An amount of a base used is preferably 2 to 5 equivalents to 1 mole of a bicycloheptenone derivative (2).
Solvents able to be used for the reaction include alcohols such as methanol, ethanol, propanol, isopropanol, butanol and t-butanol; ethers such as diethyl ether and tetrahydrofuran (THF); hydrocarbons such as benzene and toluene; acetonitrile, dimethylformamide (DMF), water, toluene, benzene and the like, or mixtures of 2 or more of these solvents.
In the aforementioned reaction, it is particularly preferable to use alcoholic solvents, that is, alcohols, or mixed solvents of alcohol and other solvents such as water and alcohol or alcohol and ether.
In the above reaction, an ester (COOR2) having a portion corresponding to an alcohol (R2OH) used or the alkoxide portion of a metal alkoxide (MOR2) used can be obtained; for example, a methyl ester is obtained with the use of methyl alcohol and an ethyl ester from ethyl alcohol.
More preferred combinations of a base and a solvent include, for example, sodium methoxide and methanol (or a mixed solvent of methanol and other solvents), sodium ethoxide and ethanol (or a mixed solvent of ethanol and other solvents), sodium hydroxide and alcohol (or a mixed solvent of alcohol and other solvents), potassium hydroxide and alcohol (or a mixed solvent of alcohol and other solvents), and potassium t-butoxide and butanol.
In the case of the use of mixed solvents or aqueous solvents, carboxylic acids (R2=H) can be obtained. Solvents used together with water are favorably alcohols and ethers. As for bases, the aforementioned hydroxides or carbonates are preferably used.
In the case of the use of metal alkoxides, it is preferable to use corresponding alcohols, as described above. It is of course possible to use other alcohols.
Preferred reaction temperatures are between xe2x88x9210xc2x0 C. and the boiling point of solvents used.
(Process 2) 
(wherein R1, R2, Q and X are as defined above.)
A bicycloheptenone derivative (2) can be obtained by hydrolysis of a bicycloheptene derivative (3) with an acid such as hydrochloric acid or sulfuric acid.
That is, a compound (2) can be obtained by hydrolyzing a compound (3) without using a solvent or with a solvent including alcohols such as methanol, ethanol and t-butanol, ethers such as diethyl ether and tetrahydrofuran (THF) or aromatic hydrocarbons such as benzene and toluene, or a mixed solvent of two or more of these solvents, at temperature between xe2x88x9210xc2x0 C. and the boiling point of solvents used.
After this, a target benzoic acid derivative can be prepared in the same way as that described in Process 1 above.
(Process 3) 
(wherein R1, R2, Q and X are as defined above.)
A Diels-Alder reaction of a cyclopentadiene derivative (4) and an ethylene derivative substituted with a hetero ring (5) gives a bicycloheptene derivative (3).
The Diels-Alder reaction can be carried out according to methods described, for example, in Tetrahedron, 42, 1741-1744 (1986) or J. Org. Chem., 26, 2066-2072 (1961).
In the above reaction, cyclopentadienes and ethylene derivatives are reacted while heating. A molar ratio of the ethylene derivatives used in the reaction is 0.5 to 10 times in equivalent, preferably 1 to 3 equivalents, to 1 mole of cyclopentadienes. The reaction is carried out at temperature between room temperature and 25xc2x0 C., more preferably between 70xc2x0 C. and 200xc2x0 C.
Although this reaction is usually carried out without solvents, solvents may be used. Examples of solvents used include aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene and dichlorobenzene; alcohols such as ethanol, n-propyl alcohol, ethylene glycol, 1,3-butanediol and ethylene glycol monomethyl ether; ethers such as dimethoxyethane, dioxane and diethylene glycol dimethyl ether, amides such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrolidone and N,N-dimethylimidazoline; hydrocarbons containing sulfur such as dimethylsulfoxide and sulfolane, and water.
The reaction proceeds more smoothly by adding a polymerization inhibitor such as hydroquinone in the presence of a base such as sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate or potassium carbonate.
After this, a target benzoic acid derivative can be produced in the same way as that in Process 2.
A compound of Formula (5), a starting material, can be prepared according to methods described, for example, in the following papers:
Chim. Ind. (Milan), 52 (1), 56 (1977): Preparation of 3-(1-propenyl)-1H-pyrrole;
Zh. Organ. Khim., 2, 417-423 (1966): Preparation of 5-(1-propenyl)-isoxazole;
J. Org. Chem., 62, 3671-3677 (1997): Preparation of 3(1-propenyl)-2-isoxazoline;
Heterocycles, 22 (11), 2475-2478 (1984): Preparation of 4(1-propenyl)pyridine; and
Heterocycles, 29(1), 103-114 (1989): Preparation of 5-(1-propenyl)-oxazole.
(Process 4) 
(wherein R1, R2, R4 and Q are as defined above.)
In the process, a 4,5-dichlorobenzoic acid derivative of Formula (1) is reacted with an excessive amount of alkane thiol of Formula R4SH (R4 is as defined above) in an appropriate inert solvent in the presence of a base, to give a 4-alkylthiobenzoic acid derivative of Formula (6).
While doing so, the reaction proceeds more smoothly under the irradiation of light (of a specified wavelength). Various light sources can be used, including sunlight, fluorescent lights, mercury lamps, arc lamps and incandescent lamps. It is preferable to carry out the reaction under inert gas atmosphere, after the reaction system is sufficiently degassed.
The reaction may sometimes proceed more smoothly by adding water of 0.1 to 5 times in equivalent to the amount of 4,5-dichlorobenzoic acid derivative (1).
Particularly preferred solvents used for this reaction are amides, such as dimethylformamide DMF), N,N-dimethylacetamide and N-methylpyrolidone. However, solvents used are not restricted to them.
Examples of bases used include hydroxides such as sodium hydroxide and potassium hydroxide; carbonates such as sodium carbonate, sodium hydrogen carbonate, potassium carbonate and potassium hydrogen carbonate; and metal alcolates such as sodium methylate, sodium etheylate and potassium t-butoxide. In this case, a salt of alkane thiol, such as sodium or potassium salt of alkane thiol, prepared from an alkane thiol and a base beforehand, can be used for the reaction.
Amounts of base and alkane thiol used are preferably 2 to 20 equivalents to that of 4,5-dichlorobenzoic acid derivative (1).
Benzoic acid derivatives of Formula (6) can be produced by isolation of Compound (7) followed by reduction, as shown in the following reaction scheme: 
To produce a compound of Formula (7), an equivalent of a compound of Formula (1) is reacted with about 1 to 3 equivalents of an alkane thiol of Formula R4SH (R4 is as defined above) in an inert solvent in the presence of an appropriate base.
In the reduction reaction from a compound of Formula (7) to a compound of Formula (6), the same alkane thiol (R4SH) as that used in the previous reaction can be used as a reducing agent. Further, other reducing agents such as hydrogen sulfide and aromatic thiols can be employed.
A compound of Formula (6) can be derived to a corresponding SO2R4 compound (8) by oxidation reaction of the SR4 group. This oxidation reaction may be carried out using an oxidizing agent including peroxides such as hydrogen peroxide, peracetic acid, perbenzoic acid and m-chloroperbenzoic acid, and hypochlorites such as sodium hypochlorite and potassium hypochlorite, in an inert solvent including water, alcohols such as methanol and ethanol organic acids such as acetic acid, and halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride. The reaction proceeds smoothly in the temperature range from 0xc2x0 C. to the boiling point of the solvent used.
Further, a SO2R4 compound (8) can be obtained by oxidation of a compound of the said Formula (7) and then a reduction reaction for dechlorination. 
(wherein R1, R2, R4 and Q are as defined above.)
A compound of Formula (9) can be produced by oxidation of a compound of Formula (7). This oxidation reaction may be carried out using an oxidizing agent including peroxides such as hydrogen peroxide, peracetic acid, perbenzoic acid and m-chloroperbenzoic acid, and hypochlorites such as sodium hypochlorite and potassium hypochlorite, in an inert solvent including water, alcohols such as methanol and ethanol, organic acids such as acetic acid, and halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride. The reaction proceeds smoothly in the temperature range from 0xc2x0 C. to the boiling point of the solvent used.
The next dechlorination of a compound of Formula (9) is carried out by such a method as catalytic hydrogenolysis using Raney nickel as a catalyst, method of using metal and metal salts such as lithium and sodium hydrogenolytic reduction with tin hydride, reduction with a metal-hydrogen complex compound such as lithium aluminum hydride, or electrolytic reduction, described in Shin Jikkenkagakukouza Vol. 14, Syntheses and Reactions of Organic Compounds [I] pages 22-30 (edited by the Chemical Society of Japan, published by Maruzen Co., Ltd.).
The compounds of the present invention, intermediates and others can be obtained with usual post-treatments after the completion of the reactions.
The structures of the compounds of the present invention, intermediates and others were determined by IR, NMR, MS and other means.
The present invention is described in more detail in reference to Examples and Reference Examples.
In Examples, of the compounds of the present invention, (1S, 4R, 5R, 6S) and (1R, 4S, 5S, 6R) isomers are represented as xe2x80x9ctransxe2x80x9d, and (1S, 4R, 5R, 6R) and (1R, 4S, 5S, 6S) isomers as xe2x80x9ccisxe2x80x9d.